Function and Expression in Pluripotency
LIF (Leukemia inhibitory factor) signaling, which maintains pluripotency in mouse embryonic stem cells, activates Sox2 downstream of the JAK-STAT signaling pathway and subsequent activation of Klf4 (a member of the family of Kruppel-like factors). Oct-4, Sox2 and Nanog positively regulate transcription of all pluripotency circuitry proteins in the LIF pathway.
NPM1, a transcriptional regulator involved in cell proliferation, individually forms complexes with Sox2, Oct4 and Nanog in embryonic stem cells. These three pluripotency factors contribute to a complex molecular network that regulates a number of genes controlling pluripotency. Sox2 binds to DNA cooperatively with Oct4 at non-palindromic sequences to activate transcription of key pluripotency factors. Surprisingly, regulation of Oct4-Sox2 enhancers can occur without Sox2, likely due to expression of other Sox proteins. However, a group of researchers concluded that the primary role of Sox2 in embryonic stem cells is controlling Oct4 expression, and they both perpetuate their own expression when expressed concurrently.
In an experiment involving mouse embryonic stem cells, it was discovered that Sox2 in conjunction with Oct4, c-Myc and Klf4 were sufficient for producing induced pluripotent stem cells. The discovery that expression of only four transcription factors was necessary to induce pluripotency allowed future regenerative medicine research to be conducted considering minor manipulations.
Loss of pluripotency is regulated by hypermethylation of some Sox2 and Oct4 binding sites in male germ cells and post-transcriptional suppression of Sox2 by miR134.
Varying levels of Sox2 affect embryonic stem cells' fate of differentiation. Sox2 inhibits differentiation into the mesendoderm germ layer and promotes differentiation into neural ectoderm germ layer. Npm1/Sox2 complexes are sustained when differentiation is induced along the ectodermal lineage, emphasizing an important functional role for Sox2 in ectodermal differentiation.
Read more about this topic: SOX2
Famous quotes containing the words function and/or expression:
“The uses of travel are occasional, and short; but the best fruit it finds, when it finds it, is conversation; and this is a main function of life.”
—Ralph Waldo Emerson (1803–1882)
“Technology is not an image of the world but a way of operating on reality. The nihilism of technology lies not only in the fact that it is the most perfect expression of the will to power ... but also in the fact that it lacks meaning.”
—Octavio Paz (b. 1914)